We previously showed that human brain ferritin (HBF) binds aluminum (Al) in vivo and in vitro and HBF isolated from Alzheimer's brain had more Al bound compared to aged matched controls (7). To further understand the role ferritin may play in Al neurotoxicity, we have studied in vitro the effect of Al on the function of human ferritin isolated from Alzheimer's (AD) and normal brain tissue, and compared the results with other mammalian ferritins. Al causes a concentration-dependent decrease in the initial rate of iron loading into apo-horse spleen and human brain ferritin and the rates were similar for ferritin isolated from both AD and normal brains. The rates of iron release of mammalian ferritins from different tissues were determined: horse spleen much greater than human liver greater than rat brain greater than human brain = rat liver ferritin. The rates of iron release of AD and normal human brain ferritin were similar and were unaffected by preloading with Al. Several mammalian ferritins were compared for their total iron uptake: horse spleen = human liver greater than human brain (normal) = human brain (AD) ferritin. In 20 mM HEPES (pH 6.0) buffer holoferritin is more resistant to precipitation by Al than apoferritin suggesting that holoferritin is a better chelator for nonferrous metal ions.